Impact of chronic transcranial random noise stimulation (tRNS) on GABAergic and glutamatergic activity markers in the prefrontal cortex of juvenile mice

Transcranial random noise stimulation (tRNS), a non-invasive neuromodulatory technique capable of altering cortical activity, has been proposed to improve the signal-to-noise ratio at the neuronal level and the sensitivity of the neurons following an inverted U-function. The aim of this study was to examine the effects of tRNS on vGLUT1 and GAD 65-67 and its safety in terms of pathological changes. For that, juvenile mice were randomly distributed in three different groups: "tRNS 1×" receiving tRNS at the density current used in humans (0.3A/m2, 20min), "tRNS 100×" receiving tRNS at two orders of magnitude higher (30.0A/m2, 20min) and "sham" (0.3A/m2, 15s). Nine tRNS sessions during 5 weeks were administered to the prefrontal cortex of awake animals. No detectable tissue macroscopic lesions were observed after tRNS sessions. Post-stimulation immunohistochemical analysis of GAD 65-67 and vGLUT1 immunoreactivity showed reduced GAD 65-67 immunoreactivity levels in the region directly beneath the electrode for tRNS 1× group with no significant effects in the tRNS 100× nor sham group. The observed results suggest an excitatory effect associated with a decrease in GABA levels in absence of major histopathological alterations providing a novel mechanistic explanation for tRNS effects.